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TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk

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Published in Laboratory Investigation. 1999, vol. 79, no. 4, p. 495-500
Abstract Injection of mouse recombinant TNF to mice induced apoptosis and detachment of the enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection. Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 microg) decreased enterocyte detachment and apoptosis, as well as villus atrophy, whereas a caspase 3 inhibitor (Z-DEVD-cmk) had no effect. The results indicate that the induction of caspases by TNF is the cause of their detachment in the lumen and of the resulting villus atrophy.
Keywords Amino Acid Chloromethyl Ketones/pharmacologyAnimalsAntigens, CD/genetics/metabolism/physiologyApoptosis/drug effects/physiologyCell Adhesion/drug effects/physiologyCysteine Proteinase Inhibitors/pharmacologyDNA FragmentationIntestinal Mucosa/cytology/drug effects/pathologyMiceMice, Inbred C57BLMice, Inbred CBAMice, KnockoutReceptors, Tumor Necrosis Factor/genetics/metabolism/physiologyReceptors, Tumor Necrosis Factor, Type IRecombinant Proteins/pharmacologyTumor Necrosis Factor-alpha/pharmacology
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PMID: 10212002
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Article (Published version) (2.7 MB) - document accessible for UNIGE members only Limited access to UNIGE
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Research group Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
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PIGUET, Pierre et al. TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk. In: Laboratory Investigation, 1999, vol. 79, n° 4, p. 495-500. https://archive-ouverte.unige.ch/unige:74361

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Deposited on : 2015-07-27

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